Global silent transmission of the class A ß-lactamase LAP-2 by plasmid transfer and clonal expansion of Klebsiella pneumoniae lineages

Abstract

BACKGROUND Narrow-spectrum antibiotics, such as narrow-spectrum β-lactams, have been pointed out as an efficient strategy to mitigate resistance and reach successful outcomes in treating enterobacterial infections. The narrow-spectrum class A β-lactamase LAP-2, conferring resistance to narrow-spectrum cephalosporins/penicillin derivatives, is spread among Enterobacteriaceae from Asia but is rarely reported in the Americas. Due to the lack of information concerning the blaLAP-2 genetic background involved with its dissemination, this study determined the blaLAP-2 genomic environment and contextualised the LAP-2-positive Klebsiella pneumoniae strains from Brazil in the current epidemiological scenario. OBJECTIVES This study characterised LAP-2-positive K. pneumoniae strains, focusing on their genetic environment and epidemiology. METHODS Whole-genome sequencing and in silico analyses were performed to identify the genetic context of blaLAP-2 in five clinical isolates from Brazil. Comparative genomics and phylogenomic analysis were conducted to investigate the transmission dynamics of blaLAP-2 globally. FINDINGS The blaLAP-2 gene was embedded in a conserved genetic module (IS3-blaLAP-2-ftsI), facilitating its dissemination among diverse Enterobacteriaceae species. The Brazilian strains harboured blaLAP-2 within a pXJ-K2 variant plasmid, a key vector in LAP-2 spread. Phylogenomic analysis revealed that, in Brazil, blaLAP-2 was carried by an ST11 K. pneumoniae lineage distinct from the Chinese lineage but globally disseminated. MAIN CONCLUSIONS This study provides insights into the epidemiology and transmission dynamics of blaLAP-2, revealing its silent spread via plasmid transfer and clonal expansion of ST11 lineages. The high transmission potential of blaLAP-2 may compromise the application of narrow-spectrum β-lactams as a viable treatment option for enterobacteria-causing infections.